CC-chemokine receptor 6 is expressed on diverse memory subsets of T cells and determines responsiveness to macrophage inflammatory protein 3 alpha

J Immunol. 1999 Jan 1;162(1):186-94.

Abstract

CC-chemokine receptor (CCR) 6 is the only known receptor for macrophage inflammatory protein (MIP)-3alpha, a CC chemokine chemotactic for lymphocytes and dendritic cells. Using anti-serum that we raised against the N-terminal residues of CCR6, we have characterized the surface expression of CCR6 on peripheral blood leukocytes and we have correlated CCR6 expression with responses to MIP-3alpha. We found that CCR6 was expressed only on memory T cells, including most alpha4beta7 memory cells and cutaneous lymphocyte-associated Ag-expressing cells, and on B cells. Accordingly, chemotaxis of T cells to MIP-3alpha was limited to memory cells. Moreover, calcium signals on T cells in response to MIP-3a were confined to CCR6-expressing cells, consistent with CCR6 being the only MIP-3alpha receptor on peripheral blood T cells. Unlike many CC chemokines, MIP-3alpha produced a calcium signal on freshly isolated T cells, and CCR6 expression was not increased by up to 5 days of treatment with IL-2 or by cross-linking CD3. Despite their surface expression of CCR6, freshly isolated B cells did not respond to MIP-3alpha. In addition to staining peripheral blood leukocytes, our anti-serum detected CCR6 on CD34+ bone marrow cell-derived dendritic cells. Our data are the first to analyze surface expression of CCR6, demonstrating receptor expression on differentiated, resting memory T cells, indicating differences in receptor signaling on T cells and B cells and suggesting that CCR6 and MIP-3alpha may play a role in the physiology of resting memory T cells and in the interactions of memory T cells, B cells, and dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chemokine CCL20
  • Chemokines, CC / physiology*
  • Flow Cytometry
  • Humans
  • Immune Sera / biosynthesis
  • Immunologic Memory*
  • Kidney / cytology
  • Leukocytes / chemistry
  • Leukocytes / immunology
  • Lymphocyte Activation
  • Macrophage Inflammatory Proteins*
  • Peptide Fragments / immunology
  • Receptors, CCR6
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / immunology
  • Staining and Labeling
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • Chemokine CCL20
  • Chemokines, CC
  • Immune Sera
  • Macrophage Inflammatory Proteins
  • Peptide Fragments
  • Receptors, CCR6
  • Receptors, Chemokine